Effect of Bariatric Surgery on Sexual Function and Sex Hormone Levels in Obese Patients: A Meta-Analysis

Effect of Bariatric Surgery on Sexual Function and Sex Hormone Levels in Obese Patients: A... Abstract Patients with a body mass index >40 kg/m2 or >35 kg/m2 with serious coexisting medical conditions are recommended to have bariatric surgery by the US National Institutes of Health. The effects of bariatric surgery on sexual function and sex hormone levels in obese patients were evaluated in this meta-analysis. The PubMed, Medline, and Cochrane databases were searched for the terms bariatric surgery, sexual function, and sex hormone to identify adult human studies published in English. The search was restricted to dates between 1 January 1990 and 1 December 2016. Two investigators independently searched the literature according to the included and excluded criteria, extracted data, and evaluated the quality of data to perform a meta-analysis. Thirty-six studies, including 1273 patients, met all criteria. The Female Sexual Function Index (FSFI) and the International Index of Erectile Function (IIEF) were used to measure female and male sexual function, respectively. After surgery, the IIEF in obese men was significantly improved, but the FSFI in obese women was only slightly improved. In obese male patients after bariatric surgery, the levels of total testosterone (TT), free testosterone (FT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormone–binding globulin (SHBG) were increased, but the levels of estradiol (E2) were decreased. In obese women, the TT, FT, and E2 were decreased, but the levels of LH, FSH, and SHBG were increased. In conclusion, this meta-analysis indicated that bariatric surgery improves sex hormone levels and sexual function in men but only slightly improves them in women. Obesity is an increasing public health problem. In 2014, 15% of women and 11% of men aged ≥18 years were obese, as revealed in the Global Health Observatory data of the World Health Organization [1]. The increasing prevalence of obesity is accompanied by comorbidities, such as diabetes, hypertension, heart disease, hyperlipidemia, and obstructive sleep apnea [2]. In addition, obesity is also associated with sexual dysfunction and infertility [3]. More than 50% of women with polycystic ovarian syndrome (PCOS) are overweight or obese [4]. Moreover, obesity has been associated with changes in several sex hormones in women and men, which may reduce sexual function [5]. Lifestyle modifications, including diet and exercise, in obese patients have been shown to reduce diabetes and heart disease [6, 7]. However, one study indicated that most of the weight lost through diet and exercise in the majority of patients is regained in the long term [8]. Bariatric surgery is another option that can achieve fast and lasting weight loss in obese patients, and bariatric surgery is associated with an improvement or resolution of obesity-related diseases. Patients with body mass index (BMI) >40 kg/m2 or >35 kg/m2 with serious complications are advised to undergo bariatric surgery [9]. Globally, the total number of bariatric surgeries increased from 344,221 cases in 2008 to 468,609 cases in 2013, and 95.7% of the procedures were laparoscopic [10]. The most commonly performed procedures are laparoscopic Roux-en-Y gastric bypass (LRYGB), laparoscopic gastric banding (LGB), laparoscopic adjustable gastric banding (LAGB), laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), adjustable gastric banding (AGB), gastric banding (GB), vertical gastric banding (VGB), biliopancreatic diversion (BPD), and silastic ring vertical gastroplasty (SRVG). More than half of bariatric surgery patients have reported sexual dysfunction (SD) [11]. The Female Sexual Function Index (FSFI) [12] and the International Index of Erectile Function (IIEF) [13] are used to measure female and male sexual function, respectively. Women with a total FSFI score ≤26 are categorized as having female sexual dysfunction (FSD). Men who score <26 on the erectile function subscale are diagnosed as having erectile dysfunction (ED). After bariatric surgery, insulin sensitivity is improved by weight loss, and sexual function is expected to improve. Some studies have shown that sexual function in obese patients is improved after bariatric surgery [5, 11, 14–21]. However, one study has shown no improvement in sexual function after LGB, with deterioration of erectile index and orgasmic function when adjusted for time [22]. Furthermore, a study has suggested that surgeons should be cautious about recommending bariatric surgery because the incidence of long-term complications after surgery is high, especially for LGB [23]. Some studies have found that obesity in men is associated with increased estrogens and reduced total testosterone (TT), free testosterone (FT), and sex hormone–binding globulin (SHBG) levels [24]. Few studies have specifically evaluated the effect of bariatric surgery on sex hormone levels in obese patients, and the results are controversial. A randomized controlled trial [19] investigated 10 obese men who accepted lifestyle interventions for 4 months and then underwent gastric bypass with a 20-month follow-up period. The study revealed that there was no impact on hormone levels or sexual function after lifestyle modifications but that TT, FT, and follicle-stimulating hormone (FSH) increased and estradiol (E2) decreased significantly after gastric bypass. Mora et al. [18] found that TT, FT, FSH, and SHBG levels increased after GB and SG. In contrast, luteinizing hormone (LH) and E2 increased, but the increase did not reach statistical significance. The relationships between bariatric surgery and type 2 diabetes mellitus (T2DM), hypertension, heart disease, and other diseases in obese patients have been given a great deal of attention. A meta-analysis found that 78% of 3188 patients with diabetes showed normalization of blood glucose after surgery [25]. A meta-analysis indicated that obese patients experience improvement or resolution of their hypertension after bariatric surgery [26]. In addition, a systematic review clearly illustrated a benefit of bariatric surgery not only on future cardiovascular risk but also on myocardial mass and diastolic function [27]. A recent survey revealed that the number of patients who experienced an improvement in SD after surgery increases exponentially in both genders [28]. Our meta-analysis aimed to obtain a global estimate of the effect of bariatric surgery on sexual function and sex hormone levels in obese patients. 1. Materials and Methods A. Data Sources Data were extracted from PubMed, Medline, and Cochrane databases by two independent investigators using the following Medical Subject Headings terms and keywords: bariatric surgery, sexual function, and sex hormone. All studies in the English language and with human subjects published from 1 January 1990 to 1 December 2016 were included. References of recent systematic reviews were used to identify other potentially relevant studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was used to depict the search strategy (Fig. 1) [29]. Figure 1. View largeDownload slide PRISMA flowchart for studies reporting on sexual function and sex hormone levels in bariatric surgery. Figure 1. View largeDownload slide PRISMA flowchart for studies reporting on sexual function and sex hormone levels in bariatric surgery. B. Study Selection All relevant studies regarding the effect of bariatric surgery on sexual function and sex hormone levels were included, and the findings were then screened and cross-checked. Differences were resolved by discussion. Any lack of information was addressed by contacting the author of the study. The included articles met the following conditions: published in English; adult patients; reported sexual function (FSFI or IIEF) and at least one sex hormone level, including TT, FT, E2, LH, FSH, SHBG, or insulin (blood samples were taken in the morning after an overnight fast and were performed in the early follicular phase of the menstrual cycle for women); follow-up time of at least ≥6 months; and results expressed parameters in terms of mean ± standard deviation. Studies reporting on fertility and pregnancy were excluded if those studies focused on body image, marital satisfaction, or sexual abuse. Publications were excluded if results were expressed as median values. C. Data Extraction An included study had to describe values of FSFI or IIEF and at least one sex hormone level, including TT, FT, E2, LH, FSH, SHBG, and insulin, among obese patients before and after bariatric surgery. Information about the following variables was systematically recorded: study design, sex, age, sample size, surgery type, baseline BMI, and follow-up time. Data describing sexual function and sex hormone levels at 12 months were extracted if the data were available from multiple time points. D. Assessment of Study Quality Considering the characteristics of all included studies, the Newcastle–Ottawa Scale (NOS) (http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp) was specifically used to assess the methodological quality of each study according to the three major domains (the selection of participants, the comparability of the groups, and the exposure ascertainment) of the scoring system. The score ranged between 0 and 9 for each study. A total score of ≥7 indicated high quality, and a total score ≤6 indicated low quality. E. Data Synthesis Continuous variables of sexual function and sex hormone levels were used as results. Summary of evaluation is expressed as the mean difference (MD) with 95% confidence intervals (CIs). P ≤ 0.05 (two-sided) was set as statistical significance. Heterogeneity was estimated with I2 statistics. If I2 > 50%, heterogeneity existed according to the Cochrane handbook [30]. If I2 > 50%, a random effects model was used, and if heterogeneity was not present, a fixed effects model was used. An Egger or Begg test was used to assess publication bias for the included studies >10. Meta-analyses were performed in Review Manager (RevMan version 5.3.5; The Nordic Cochrane Centre, Copenhagen, Denmark) [31] and Stata (version 12.0; StataCorp, College Station, TX) software programs. 2. Results A. Study Selection We searched and then screened 139 potential publications according to the PRISMA guidelines [29]. Seventy-nine publications were excluded because 65 studies did not discuss sexual function or sex hormone levels in obese patients who underwent bariatric surgery, 11 studies were not based on human studies, and 3 studies were published in French. Sixty potential articles have been carried out full-length paper evaluation. However, 12 of these studies were excluded because they reported only sexual function or sex hormone levels result either before or after surgery, and 4 studies were excluded because they used the Impact of Weight on Quality of Life–Lite measure of SD. Moreover, 3 studies were excluded because they used the Brief Male Sexual Function Inventory to evaluate male sexual function, and 5 studies were excluded because the results were expressed as median values. Ultimately, 36 studies were included in the meta-analysis [5, 11, 14–22, 24, 32–55], and the search strategy is shown in Fig. 1. The full text of 12 articles was assessed for the effect of lifestyle modifications on sexual function and sex hormone levels in obese patients [56–66] (Supplemental Table 1 and Supplemental Fig. 1). B. Study Characteristics There were 21 prospective, 2 retrospective, 3 cohort, and 2 observational studies included in our meta-analysis. Table 1 shows the main characteristics of all included studies. Among the studies, 1273 obese patients were evaluated before and after bariatric surgery. The following types of surgery were performed (the numbers in parentheses represent the number of included studies): RYGB (17), BPD (8), LAGB (5), SG (5), LGB (5), LSG (4), LRYGB (4), GB (3), VBG (2), AGB (2), and SRVG (1). Some studies [11, 14, 16, 18, 20, 24, 34–36, 38, 40, 50, 51, 53] included more than one method of surgery. The time to postoperative follow-up ranged from 1 to 115 months. The NOS quality scores of the studies ranged from 6 to 9. Table 1. Studies Included in the Meta-Analysis Study  Design  N  Sex  Mean Age (y)  Study Procedures  Baseline BMI (kg/m2)  Follow-Up (mo)  Outcome Indicators  Ernst et al.,32 2013  N/A  36  F  41.2  RYGB  44.5 ± 0.8  12  3, 4, 8  Assimakopoulos et al.,14 2013  Prospective study  59  F  36  BPD, RYGB, SG  51.9 ± 9.92  12  2  Bond et al.,11 2011  Cohort study  54  F  43.3  LAGB, RYGB  45.1 ± 6.8  6  2  Hernández et al.,15 2012  Prospective study  80  F  43.5  BPD  52.2 ± 8.2  12  2  Olivera et al.,16 2012  Prospective cohort study  36  F  41.3  RYGB, LAGB, LSG  45.76 ± 6.48  37  2  Legro et al.,17 2012  Prospective cohort study  29  F  34.5  RYGB  49 ± 73  12  2, 3, 5, 8  Mora et al.,18 2013  Prospective study  39  M  43.5  LRYGB, LSG  46.90 ± 7.77  12  1, 3, 4, 5, 6, 7, 8  Reis et al.,19 2015  Prospective randomized controlled study  10  M  39.3  GB  55.7 ± 7.8  24  1, 3, 4, 5, 6, 7  Rosenblatt et al.,33 2012  Prospective cohort study  23  M  47.5  RYGB  58.1 ± 12.1  115  1, 3, 4, 5, 6, 7 8, 9  Ranasinghe et al.,22 2010  Retrospective study  34  M  52.8  LGB  47.3 ± 12.67  31  1  Sarwer et al.,34 2014  Prospective cohort study  98  F  41  RYGB, LAGB  44.5 (41.4, 49.7)  12  2, 3, 5, 6, 7, 8  Goitein et al.,20 2015  N/A  34  F  38.4  LSG, LYRGB  44.4 ± 5.5  6  2  Kun et al.,21 2014  Retrospective cohort study  39  M  45.2  RYGB  41.2 ± 5.8  12  1  Sarwer et al.,5 2015  Prospective cohort study  32  M  48  RYGB  45.1 (42.0, 52.2)  12  1, 3, 4, 6, 8  Escobar-Morreale et al.,35 2005  Prospective study  12  F  29.8  BPD, LGB  50.7 ± 7.1  12  3, 4  Rochester et al.,36 2009  Observational cohort study  25  F  36.6  BPD, GB  47.3 ± 5.2  6  6, 7  Alagna et al.,37 2006  N/A  20  M  42  BPD  47.3 ± 13.1  12  3, 5, 6, 7  Calderón et al.,38 2014  N/A  20  M  38  LGB  50.4 ± 8.7  12  3, 4, 5, 6, 7, 8, 9  Calderón et al.,38 2014  N/A  15  M  41  SG, AGB  42.9 ± 2.7  12  3, 4, 5, 6, 7, 8  Hammoud et al.,39 2009  Cohort study  22  M  48.9  RYGB  46.2 ± 0.9  24  3, 4, 5  Pellitero et al.,40 2012  Observational study  33  M  40.5  RYGB, SG  50.3 ± 6.1  12  3, 4, 5, 8  Samavat et al.,24 2014  Prospective cohort study  55  M  42.3  RYGB, LAGB, BPD, SG  46.6 ± 7.4  12  3, 5, 6, 7, 8  Globerman et al.,41 2005  N/A  17  M  38.2  SRVG  44.3 ± 1.7  12  3, 4, 6, 7  Woodard et al.,42 2012  N/A  64  M  48.1  RYGB  48.2 ± 12  12  3  Bastounis et al.,43 1998  Prospective study  19  M  34.7  VBG  57.1 ± 7.4  12  3, 4, 5, 6, 7, 8, 9  Bastounis et al.,43 1998  Prospective study  38  F  34.3  VBG  56.7 ± 7.7  12  3, 4, 5, 6, 7, 8, 9  Legro et al.,44 2015  Prospective cohort study  6  M  37.5  RYGB  48 ± 7  12  5, 8  Samavat et al.,45 2014  Prospective study  76  M  42  LRYGB  47.7 ± 8.2  9  3, 4, 5, 6, 7, 8  Kopp et al.,46 2014  Prospective study  43  F  41  VBG  48 ± 7  17  3, 8, 9  Mihalca et al.,47 2014  Prospective study  28  M  43.1  LSG  50.1 ± 11.19  6  3, 6, 8  Turkmen et al.,48 2014  N/A  9  F  31.4  RYGB  47.2 ± 8.85  12  3, 8  Mingrone et al.,49 2002  Prospective randomized controlled study  15  M  30 to 45  BPD  48.0 ± 5.4  12  8, 9  Mingrone et al.,49 2002  Prospective randomized controlled study  31  F  30 to 45  BPD  48.3 ± 6.3  12  8, 9  Botella-Carretero et al.,50 2013  Prospective study  20  M  40  BPD, LGB, AGB  47.05 ± 5.99  6  3, 4, 5, 6, 7, 8, 9  Aarts et al.,51 2014  Observational study  24  M  43.1  LAGB, LRYGB  46.1 ± 1.3  12  3, 4, 5, 6, 7, 8  Bekaert et al.,52 2015  Cohort study  14  M  51  GB  45.0 ± 8.0  24  3, 4, 5  Boonchaya-Anant et al.,53 2016  Prospective study  29  M  30.8  RYGB, SG  56.8 ± 11.7  6  3, 4, 5, 8  Eid et al.,54 2014  Prospective study  14  F  36.3  RYGB  44.8 ± 1.6  12  3, 4, 6, 7  Dixon et al.,55 2002  N/A  42  F  34  LGB  44.9 ± 7.7  12  3, 8, 9  Study  Design  N  Sex  Mean Age (y)  Study Procedures  Baseline BMI (kg/m2)  Follow-Up (mo)  Outcome Indicators  Ernst et al.,32 2013  N/A  36  F  41.2  RYGB  44.5 ± 0.8  12  3, 4, 8  Assimakopoulos et al.,14 2013  Prospective study  59  F  36  BPD, RYGB, SG  51.9 ± 9.92  12  2  Bond et al.,11 2011  Cohort study  54  F  43.3  LAGB, RYGB  45.1 ± 6.8  6  2  Hernández et al.,15 2012  Prospective study  80  F  43.5  BPD  52.2 ± 8.2  12  2  Olivera et al.,16 2012  Prospective cohort study  36  F  41.3  RYGB, LAGB, LSG  45.76 ± 6.48  37  2  Legro et al.,17 2012  Prospective cohort study  29  F  34.5  RYGB  49 ± 73  12  2, 3, 5, 8  Mora et al.,18 2013  Prospective study  39  M  43.5  LRYGB, LSG  46.90 ± 7.77  12  1, 3, 4, 5, 6, 7, 8  Reis et al.,19 2015  Prospective randomized controlled study  10  M  39.3  GB  55.7 ± 7.8  24  1, 3, 4, 5, 6, 7  Rosenblatt et al.,33 2012  Prospective cohort study  23  M  47.5  RYGB  58.1 ± 12.1  115  1, 3, 4, 5, 6, 7 8, 9  Ranasinghe et al.,22 2010  Retrospective study  34  M  52.8  LGB  47.3 ± 12.67  31  1  Sarwer et al.,34 2014  Prospective cohort study  98  F  41  RYGB, LAGB  44.5 (41.4, 49.7)  12  2, 3, 5, 6, 7, 8  Goitein et al.,20 2015  N/A  34  F  38.4  LSG, LYRGB  44.4 ± 5.5  6  2  Kun et al.,21 2014  Retrospective cohort study  39  M  45.2  RYGB  41.2 ± 5.8  12  1  Sarwer et al.,5 2015  Prospective cohort study  32  M  48  RYGB  45.1 (42.0, 52.2)  12  1, 3, 4, 6, 8  Escobar-Morreale et al.,35 2005  Prospective study  12  F  29.8  BPD, LGB  50.7 ± 7.1  12  3, 4  Rochester et al.,36 2009  Observational cohort study  25  F  36.6  BPD, GB  47.3 ± 5.2  6  6, 7  Alagna et al.,37 2006  N/A  20  M  42  BPD  47.3 ± 13.1  12  3, 5, 6, 7  Calderón et al.,38 2014  N/A  20  M  38  LGB  50.4 ± 8.7  12  3, 4, 5, 6, 7, 8, 9  Calderón et al.,38 2014  N/A  15  M  41  SG, AGB  42.9 ± 2.7  12  3, 4, 5, 6, 7, 8  Hammoud et al.,39 2009  Cohort study  22  M  48.9  RYGB  46.2 ± 0.9  24  3, 4, 5  Pellitero et al.,40 2012  Observational study  33  M  40.5  RYGB, SG  50.3 ± 6.1  12  3, 4, 5, 8  Samavat et al.,24 2014  Prospective cohort study  55  M  42.3  RYGB, LAGB, BPD, SG  46.6 ± 7.4  12  3, 5, 6, 7, 8  Globerman et al.,41 2005  N/A  17  M  38.2  SRVG  44.3 ± 1.7  12  3, 4, 6, 7  Woodard et al.,42 2012  N/A  64  M  48.1  RYGB  48.2 ± 12  12  3  Bastounis et al.,43 1998  Prospective study  19  M  34.7  VBG  57.1 ± 7.4  12  3, 4, 5, 6, 7, 8, 9  Bastounis et al.,43 1998  Prospective study  38  F  34.3  VBG  56.7 ± 7.7  12  3, 4, 5, 6, 7, 8, 9  Legro et al.,44 2015  Prospective cohort study  6  M  37.5  RYGB  48 ± 7  12  5, 8  Samavat et al.,45 2014  Prospective study  76  M  42  LRYGB  47.7 ± 8.2  9  3, 4, 5, 6, 7, 8  Kopp et al.,46 2014  Prospective study  43  F  41  VBG  48 ± 7  17  3, 8, 9  Mihalca et al.,47 2014  Prospective study  28  M  43.1  LSG  50.1 ± 11.19  6  3, 6, 8  Turkmen et al.,48 2014  N/A  9  F  31.4  RYGB  47.2 ± 8.85  12  3, 8  Mingrone et al.,49 2002  Prospective randomized controlled study  15  M  30 to 45  BPD  48.0 ± 5.4  12  8, 9  Mingrone et al.,49 2002  Prospective randomized controlled study  31  F  30 to 45  BPD  48.3 ± 6.3  12  8, 9  Botella-Carretero et al.,50 2013  Prospective study  20  M  40  BPD, LGB, AGB  47.05 ± 5.99  6  3, 4, 5, 6, 7, 8, 9  Aarts et al.,51 2014  Observational study  24  M  43.1  LAGB, LRYGB  46.1 ± 1.3  12  3, 4, 5, 6, 7, 8  Bekaert et al.,52 2015  Cohort study  14  M  51  GB  45.0 ± 8.0  24  3, 4, 5  Boonchaya-Anant et al.,53 2016  Prospective study  29  M  30.8  RYGB, SG  56.8 ± 11.7  6  3, 4, 5, 8  Eid et al.,54 2014  Prospective study  14  F  36.3  RYGB  44.8 ± 1.6  12  3, 4, 6, 7  Dixon et al.,55 2002  N/A  42  F  34  LGB  44.9 ± 7.7  12  3, 8, 9  Outcome indicators: (1) IIEF, (2) FSFI, (3) TT, (4) FT, (5) E2, (6) LH, (7) FSH, (8) SHBG, (9) insulin. View Large C. Bariatric Surgery and Sexual Function Of the 36 studies, 5 studies [5, 18, 19, 21, 22] reported the IIEF of obese men before and after bariatric surgery in 154 of 1273 patients. Based on a fixed effects model, meta-analysis showed a significant increase in IIEF score (MD = 4.84; 95% CI, 2.92 to 6.75; P < 0.00001; Fig. 2A). Seven studies [11, 14–17, 20, 34] reported the FSFI score of obese women before and after bariatric surgery in 369 of 1273 patients. Based on a random effects model, meta-analysis showed that the FSFI score after surgery was higher than the preoperative score, but this increase did not reach statistical significance (MD = 4.10; 95% CI, −0.28 to 8.48; P = 0.07; Fig. 2B). Moreover, assessments of the effects of lifestyle-mediated weight loss on sexual function in obese men showed that bariatric surgery was associated with a greater increase in IIEF than lifestyle modification, but this increase did not reach statistical significance (Supplemental Fig. 2). Figure 2. View largeDownload slide (A) Forest plot of the mean difference of the IIEF in men before and after bariatric surgery. (B) Forest plot of the mean difference of the FSFI in women before and after bariatric surgery. Figure 2. View largeDownload slide (A) Forest plot of the mean difference of the IIEF in men before and after bariatric surgery. (B) Forest plot of the mean difference of the FSFI in women before and after bariatric surgery. D. Bariatric Surgery and Sex Hormone Levels in Obese Men Information about the TT, FT, and E2 levels in the obese men before and after bariatric surgery was available in 18, 12, and 12 studies, respectively. Moreover, data on the LH, FSH, and SHBG levels were available in 12, 11, and 14 studies, respectively. Seventeen studies [5, 18, 19, 33, 37–43, 45, 47, 50–53] reported TT levels in obese men before and after bariatric surgery in 560 of the 1273 patients. Based on a random effects model, meta-analysis showed a significant increase in post–bariatric surgery TT levels (MD = 8.30; 95% CI, 6.92 to 9.68; P < 0.00001; Fig. 3A). Twelve studies [5, 18, 19, 33, 38, 40, 41, 43, 50–53] reported FT levels in obese men before and after bariatric surgery in 295 of 1273 patients. Using a random effects model, meta-analysis showed a significant increase in FT levels (MD = 16.06; 95% CI, 9.33 to 22.79; P < 0.00001; Fig. 3B). Twelve studies [18, 19, 24, 33, 37, 38, 40, 43, 44, 51–53] reported E2 levels in obese men before and after bariatric surgery in 294 of 1273 patients. Based on a random effects model, meta-analysis showed significantly lower E2 levels (MD = −4.49; 95% CI, −6.97 to −2.02; P = 0.0004; Fig. 3C). Twelve studies [18, 19, 24, 33, 37, 38, 41, 43, 45, 47, 50, 51] reported LH levels in obese men before and after bariatric surgery in 353 of 1273 patients. Based on a random effects model, meta-analysis showed a significant increase in LH levels (MD = 1.14; 95% CI, 0.75 to 1.52; P < 0.00001; Fig, 3D). Eleven studies [18, 19, 24, 33, 37, 38, 41, 43, 45, 50, 51] reported FSH levels in obese men before and after surgery in 325 of 1273 patients. Based on a fixed effects model, meta-analysis showed a significant increase in FSH levels (MD = 1.07; 95% CI, 0.75 to 1.40; P < 0.00001; Fig. 3E). Fourteen studies [5, 18, 24, 33, 38, 40, 43–45, 47, 49–51, 53] reported SHBG levels in obese men before and after bariatric surgery in 421 of the 1273 patients. Based on a random effects model, meta-analysis showed a significant increase in SHBG levels (MD = 22.32; 95% CI, 16.12 to 28.51; P < 0.00001; Fig. 3F). Five studies [33, 38, 43, 49, 50] reported insulin levels in obese men before and after bariatric surgery in 112 of 1273 patients. Based on a random effects model, meta-analysis showed a significant decrease in insulin levels (MD = −138.97; 95% CI, −181.82 to −96.12; P < 0.00001; Fig. 3G). When we considered data for TT, FT, E2, SHBG, and insulin levels, bariatric surgery showed a greater improvement than lifestyle interventions (Supplemental Fig. 3). Figure 3. View largeDownload slide (A) Forest plot of the mean difference in TT levels in men before and after bariatric surgery. (B) Forest plot of the mean difference in FT levels in men before and after bariatric surgery. (C) Forest plot of the mean difference in E2 levels in men before and after bariatric surgery. (D) Forest plot of the mean difference in LH levels in men before and after bariatric surgery. (E) Forest plot of the mean difference in FSH levels in men before and after bariatric surgery. (F) Forest plot of the mean difference in SHBG levels in men before and after bariatric surgery. (G) Forest plot of the mean difference in insulin levels in men before and after bariatric surgery. Figure 3. View largeDownload slide (A) Forest plot of the mean difference in TT levels in men before and after bariatric surgery. (B) Forest plot of the mean difference in FT levels in men before and after bariatric surgery. (C) Forest plot of the mean difference in E2 levels in men before and after bariatric surgery. (D) Forest plot of the mean difference in LH levels in men before and after bariatric surgery. (E) Forest plot of the mean difference in FSH levels in men before and after bariatric surgery. (F) Forest plot of the mean difference in SHBG levels in men before and after bariatric surgery. (G) Forest plot of the mean difference in insulin levels in men before and after bariatric surgery. E. Bariatric Surgery and Sex Hormone Levels in Obese Women There are limited studies on sex hormone levels in obese women who underwent bariatric procedures. Information about TT, FT, and E2 levels in obese women was available in 8, 4, and 2 studies, respectively. In addition, data for LH, FSH, and SHBG levels were usable in 4, 4, and 7 studies, respectively. In total, we retrieved 8 studies [32, 34, 35, 43, 46, 48, 54, 55] reporting TT levels in obese women preoperatively and postoperatively in 291 of 1273 patients. Based on a random effects model, meta-analysis indicated a significant decrease in postoperative TT levels (MD = −0.71; 95% CI, −0.84 to −0.58; P < 0.00001; Fig. 4A). Four studies [32, 35, 43, 54] reported FT levels in obese women before and after surgery in 100 of 1273 patients. Based on a random effects model, meta-analysis indicated a decrease in the postsurgical FT levels, but this decrease did not reach statistical significance (MD = −13.65; 95% CI, −28.82 to 1.53; P = 0.08; Fig. 4B). Two studies [34, 43] assessed E2 levels in obese women before and after bariatric surgery in 136 of 1273 patients. Based on a fixed effects model, the meta-analysis indicated a significant decrease in postoperative E2 levels (MD = −25.13; 95% CI, −36.93 to −13.32; P < 0.0001; Fig. 4C). Four studies [34, 36, 43, 54] evaluated LH levels in obese women before and after surgery in 156 of 1273 patients. Based on a random effects model, meta-analysis showed significantly increased LH levels (MD = 5.73; 95% CI, 0.15 to 11.30; P = 0.04; Fig. 4D). Four studies [34, 36, 43, 54] reported preoperative and postoperative FSH levels in obese women in 156 of 1273 patients. Based on a random effects model, meta-analysis showed a significant increase in FSH levels (MD = 3.79; 95% CI, 0.71 to 6.88; P = 0.02; Fig. 4E). However, the FSH levels in obese women showed a significant reduction after lifestyle modification (Supplemental Fig. 4D). Seven studies [32, 34, 43, 46, 48, 49, 55] assessed SHBG levels in obese women before and after bariatric surgery in 296 of 1273 patients. Based on a random effects model, meta-analysis showed a significant increase in SHBG levels (MD = 31.84; 95% CI, 20.24 to 43.44; P < 0.00001; Fig. 4F). Four studies [43, 46, 49, 55] reported insulin levels in obese women before and after bariatric surgery in 154 of 1273 patients. Based on a random effects model, meta-analysis reported a significant decrease in insulin levels (MD = −93.36; 95% CI, −119.86 to −66.86; P < 0.00001; Fig. 4G). When we considered data for TT, LH, SHBG, and insulin levels in obese women, both lifestyle intervention and bariatric surgery showed an improvement, but bariatric surgery was significantly more effective than lifestyle intervention (Supplemental Fig. 4A, 4B, 4C, and 4E). Figure 4. View largeDownload slide (A) Forest plot of the mean difference in TT levels in women before and after bariatric surgery. (B) Forest plot of the mean difference in FT levels in women before and after bariatric surgery. (C) Forest plot of the mean difference in E2 levels in women before and after bariatric surgery. (D) Forest plot of the mean difference in LH levels in women before and after bariatric surgery. (E) Forest plot of the mean difference in FSH levels in women before and after bariatric surgery. (F) Forest plot of the mean difference in SHBG levels in women before and after bariatric surgery. (G) Forest plot of the mean difference in insulin levels in women before and after bariatric surgery. (H) Forest plot of the mean difference in TT levels in women with PCOS before and after bariatric surgery. (I) Forest plot of the mean difference in FT levels in women with PCOS before and after bariatric surgery. Figure 4. View largeDownload slide (A) Forest plot of the mean difference in TT levels in women before and after bariatric surgery. (B) Forest plot of the mean difference in FT levels in women before and after bariatric surgery. (C) Forest plot of the mean difference in E2 levels in women before and after bariatric surgery. (D) Forest plot of the mean difference in LH levels in women before and after bariatric surgery. (E) Forest plot of the mean difference in FSH levels in women before and after bariatric surgery. (F) Forest plot of the mean difference in SHBG levels in women before and after bariatric surgery. (G) Forest plot of the mean difference in insulin levels in women before and after bariatric surgery. (H) Forest plot of the mean difference in TT levels in women with PCOS before and after bariatric surgery. (I) Forest plot of the mean difference in FT levels in women with PCOS before and after bariatric surgery. Subgroup analysis with PCOS, a common complication among obese patients, was performed in obese women. In three studies [35, 48, 54], TT levels in 62 obese women with PCOS before and after bariatric surgery showed a significant decrease (MD = −0.69; 95% CI, −1.19 to −0.18; P = 0.008; Fig. 4H), but the decrease was not significant compared with that of all included obese women. Two studies [35, 54] showed a greater reduction of FT levels in obese women with PCOS than in all included obese women, but this reduction did not reach statistical significance (MD = −23.58; 95% CI, −50.03 to 2.88; P = 0.08; Fig. 4I). Because only one of three studies reported LH, FSH, and SHBG levels in obese women with PCOS before and after bariatric surgery, the data were insufficient to conduct subgroup analyses. F. Publication Bias Assessment Publication bias was assessed by Egger publication bias plots in the meta-analysis regarding the changes in TT (18 studies), FT (12 studies), and E2 levels (12 studies) in obese men (Fig. 5A, 5B, and 5C). The P values of the Begg and Egger tests for TT (0.484 and 0.541, respectively), FT (0.246 and 0.111, respectively), and E2 (0.760 and 0.515, respectively) suggested that there was no significant publication bias. Similarly, publication bias was evaluated by Egger publication bias plots in the meta-analysis regarding the changes in LH (12 studies), FSH (11 studies), and SHBG levels (14 studies) in obese men (Fig. 5D, 5E, and 5F). The P values of the Begg and Egger tests for LH (0.428 and 0.668, respectively), FSH (0.537 and 0.142, respectively), and SHBG (0.373 and 0.002, respectively), suggested a lack of significant publication bias, except for the Egger test of SHBG. The reasons for different statistical significances between these two test methods may be small study size, including SHBG, or the number of included studies. Figure 5. View largeDownload slide (A) Egger test assessing publication bias for TT levels in obese men. (B) Egger test assessing publication bias for FT levels in obese men. (C) Egger test assessing publication bias for E2 levels in obese men. (D) Egger test assessing publication bias for LH levels in obese men. (E) Egger test assessing publication bias for FSH levels in obese men. (F) Egger test assessing publication bias for SHBG levels in obese men. Figure 5. View largeDownload slide (A) Egger test assessing publication bias for TT levels in obese men. (B) Egger test assessing publication bias for FT levels in obese men. (C) Egger test assessing publication bias for E2 levels in obese men. (D) Egger test assessing publication bias for LH levels in obese men. (E) Egger test assessing publication bias for FSH levels in obese men. (F) Egger test assessing publication bias for SHBG levels in obese men. 3. Discussion Our meta-analysis showed that the IIEF in obese men and the FSFI in obese women improved after bariatric surgery, but the improvement was statistically significant only in men. These results were consistent with most current systematic reviews of changes in sexual dysfunction after bariatric surgery [28]. The current meta-analysis showed a significant increase in TT, FT, LH, FSH, and SHBG levels and a reduction in E2 levels after bariatric surgery in obese men. In contrast, the TT and E2 levels in obese women significantly decreased, whereas LH, FSH, and SHBG levels significantly increased. The FT levels were also decreased in obese women, but these decreases were not significant. The normalization of sex hormones may be one of the mechanisms contributing to the advantageous effects of surgery in morbid obesity patients. The relationship between the improvement of sexual dysfunction and the sex hormone changes did not achieve consensus. Hammoud et al. [39] found that changes in sex hormones and sexual function improve insulin resistance and inflammation, and they also reported that resolution of diabetes and hypertension occurs after RYGB. Our meta-analysis suggested that bariatric surgery is related to increased insulin sensitivity in both sexes, which may be one of the factors contributing to the improvement of sex hormone levels. A previous study [50] has reported that circulating testosterone in obese men increases after BPD, LGB, or AGB in parallel with a decrease in insulin resistance. However, no studies have reported the independent contribution of each factor. Ranasinghe et al. [22] found that obese male patients displayed elevated TT, FT, and SHBG levels and improved IIEF scores but that erectile function scores were reduced after LGB, suggesting incomplete functional restoration. Relapsing obesity and recurring comorbidities might explain such an outcome. Two prospective cohort studies [17, 34] have shown no statistical evidence of the changes in FSFI and hormones after surgery by correlation of regression. However, a prospective observational study [18] found that the increase in the IIEF score at 1 year after surgery was beyond the parallel improvement of hormone levels by a multivariate regression. It is important to note that it is difficult to account for all risk factors that may contribute to sexual function, such as psychological factors and metabolic changes, when determining causality. PCOS is a common endocrine disorder in women of reproductive age. A recent study [67] has shown that surgically induced weight loss not only may reduce hirsutism in women but also may resolve menstrual and ovulatory dysfunction in severely obese patients with PCOS after bariatric surgery. Consistently, our meta-analysis showed sustained and marked weight loss after bariatric surgery with decreases in TT and FT levels, although FT levels only showed a trend, possibly because of the limited quantity of the included studies. These effects might also contribute to restoration of fertility in these women. A previous study reported that weight loss by surgery may improve fertility rates in women [68], and it also suggested that pregnancy is delayed 1 to 2 years after bariatric surgery with proper nutritional and obstetric support. Significant increases in TT, FT, FSH, and SHBG levels have the potential to improve fertility in severely obese men. However, studies evaluating spermatogenesis after surgery have had inconsistent results. Some studies have suggested adverse effects on semen parameters [69–71], whereas some prospective studies have performed serial semen analyses and showed normal ranges for most parameters [19, 44]. A more recent study [72] has shown that sperm concentration is increased in men with azoospermia and oligospermia after surgery, suggesting that weight loss may improve sperm quality. Weight loss alone may be helpful in obesity-associated SD and is strongly recommended for the management of obesity. Lifestyle interventions that include diet and exercise have a short-term effect because weight loss is difficult to obtain by lifestyle modifications, and the weight is easily regained when the lifestyle interventions are not sustained [8, 73]. Bariatric surgery is a better and longer-lasting weight loss alternative for severely obese patients. Our meta-analysis indicated that bariatric surgery is associated with a greater increase in TT, FT, and SHBG levels and a greater decrease in E2 than lifestyle interventions in obese men. In obese women, however, our meta-analysis showed that levels of TT, FT, and E2 after bariatric surgery are more significantly decreased and that the levels of LH, FSH, and SHBG are more significantly increased in comparison with lifestyle modifications. These results may be caused by the greater weight loss achieved by surgery. This meta-analysis was not without limitations. Several limitations that prevent achievement of definite conclusions should be considered. First, there was significant heterogeneity in the outcome analyses, except for IIEF and FSH in men and E2 in women. This heterogeneity may result from the absence of randomized controlled trials, different research designs, and variable research populations. Second, another limitation was the patient self-reporting, which was completed before and after surgery, because patients may have felt embarrassed when completing the sexual function questionnaires. Third, our meta-analysis measured SD only by IIEF in men and by FSFI in women, but our meta-analysis did not include the Brief Male Sexual Function Inventory [74], which consists of an 11-item questionnaire. Also, our meta-analysis did not include the Impact of Weight on Quality of Life-Lite, which takes into account other aspects of self-esteem and work [75]. Fourth, the fact that hormonal assays and reference values often are not comparable imposed a limitation on the generalization of our results. Fifth, we extracted the results at the 12-month time point only if parameters were evaluated at several different time points, which provided a conservative estimate of the effect of bariatric surgery on sexual function and sex hormones. The follow-up period after bariatric surgery in many studies was short, and the possibility of a relapse of obesity-associated sexual dysfunction and changes in sex hormone levels in the long term was not explored. A limitation to this method was that the full effect of bariatric surgery on sexual function and sex hormones may not have been realized. Finally, the small sample size of some studies was a limitation that especially affected the studies in women and the studies addressing the changes in sexual function after bariatric surgery. In conclusion, this meta-analysis showed that bariatric surgery significantly improves sexual function in men but that a more limited degree of improvement is achieved in women. In obese male patients who underwent bariatric surgery, the levels of the sex hormones TT, FT, LH, FSH, and SHBG significantly increased, and the level of E2 decreased. In obese female patients, the levels of the sex hormones TT, FT, and E2 decreased, but the levels of LH, FSH, and SHBG increased. Future studies should be performed to elucidate the mechanism of the improved sexual function in obese patients after bariatric surgery. Because of the limited quality and quantity of the included studies, more high-quality studies are needed to verify our conclusion about the sex hormone levels in obese female patients. Abbreviations: AGB adjustable gastric banding BMI body mass index BPD biliopancreatic diversion CI confidence interval E2 estradiol ED erectile dysfunction FSD female sexual dysfunction FSFI Female Sexual Function Index FSH follicle-stimulating hormone FT free testosterone GB gastric banding IIEF International Index of Erectile Function LAGB laparoscopic adjustable gastric banding LGB laparoscopic gastric banding LH luteinizing hormone LRYGB laparoscopic Roux-en-Y gastric bypass LSG laparoscopic sleeve gastrectomy MD mean difference NOS Newcastle–Ottawa Scale PCOS polycystic ovarian syndrome PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analysis RYGB Roux-en-Y gastric bypass SD sexual dysfunction SG sleeve gastrectomy SHBG sex hormone–binding globulin SRVG silastic ring vertical gastroplasty T2DM type 2 diabetes mellitus TT total testosterone VGB vertical gastric banding. Acknowledgments Financial Support: Natural Science Foundation of China (nos. 81770848 and 81170774) to J.W., Natural Science Foundation of Fujian Province (nos. 2015Y0008 and 2016Y9006) to J.W., and Fujian provincial health system in the youth personnel training project financing plan (2014-ZQN-ZD-1) to J.W. Disclosure Summary: The authors have nothing to disclose. References and Notes 1. World Health Organization. Obesity and overweight fact sheet. World Health Organization Web site. http://www.who.int/mediacentre/factsheets/fs311/en/. Accessed 15 July 2016. 2. Janik MR, Bielecka I, Paśnik K, Kwiatkowski A, Podgórska L. Female sexual function before and after bariatric surgery: a cross-sectional study and review of literature. Obes Surg . 2015; 25( 8): 1511– 1517. Google Scholar CrossRef Search ADS PubMed  3. Mozafari M, Khajavikhan J, Jaafarpour M, Khani A, Direkvand-Moghadam A, Najafi F. Association of body weight and female sexual dysfunction: a case control study. 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Google Scholar CrossRef Search ADS PubMed  Copyright © 2018 Endocrine Society This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/). http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of the Endocrine Society Oxford University Press

Effect of Bariatric Surgery on Sexual Function and Sex Hormone Levels in Obese Patients: A Meta-Analysis

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Copyright © 2018 Endocrine Society
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2472-1972
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10.1210/js.2017-00233
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Abstract

Abstract Patients with a body mass index >40 kg/m2 or >35 kg/m2 with serious coexisting medical conditions are recommended to have bariatric surgery by the US National Institutes of Health. The effects of bariatric surgery on sexual function and sex hormone levels in obese patients were evaluated in this meta-analysis. The PubMed, Medline, and Cochrane databases were searched for the terms bariatric surgery, sexual function, and sex hormone to identify adult human studies published in English. The search was restricted to dates between 1 January 1990 and 1 December 2016. Two investigators independently searched the literature according to the included and excluded criteria, extracted data, and evaluated the quality of data to perform a meta-analysis. Thirty-six studies, including 1273 patients, met all criteria. The Female Sexual Function Index (FSFI) and the International Index of Erectile Function (IIEF) were used to measure female and male sexual function, respectively. After surgery, the IIEF in obese men was significantly improved, but the FSFI in obese women was only slightly improved. In obese male patients after bariatric surgery, the levels of total testosterone (TT), free testosterone (FT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormone–binding globulin (SHBG) were increased, but the levels of estradiol (E2) were decreased. In obese women, the TT, FT, and E2 were decreased, but the levels of LH, FSH, and SHBG were increased. In conclusion, this meta-analysis indicated that bariatric surgery improves sex hormone levels and sexual function in men but only slightly improves them in women. Obesity is an increasing public health problem. In 2014, 15% of women and 11% of men aged ≥18 years were obese, as revealed in the Global Health Observatory data of the World Health Organization [1]. The increasing prevalence of obesity is accompanied by comorbidities, such as diabetes, hypertension, heart disease, hyperlipidemia, and obstructive sleep apnea [2]. In addition, obesity is also associated with sexual dysfunction and infertility [3]. More than 50% of women with polycystic ovarian syndrome (PCOS) are overweight or obese [4]. Moreover, obesity has been associated with changes in several sex hormones in women and men, which may reduce sexual function [5]. Lifestyle modifications, including diet and exercise, in obese patients have been shown to reduce diabetes and heart disease [6, 7]. However, one study indicated that most of the weight lost through diet and exercise in the majority of patients is regained in the long term [8]. Bariatric surgery is another option that can achieve fast and lasting weight loss in obese patients, and bariatric surgery is associated with an improvement or resolution of obesity-related diseases. Patients with body mass index (BMI) >40 kg/m2 or >35 kg/m2 with serious complications are advised to undergo bariatric surgery [9]. Globally, the total number of bariatric surgeries increased from 344,221 cases in 2008 to 468,609 cases in 2013, and 95.7% of the procedures were laparoscopic [10]. The most commonly performed procedures are laparoscopic Roux-en-Y gastric bypass (LRYGB), laparoscopic gastric banding (LGB), laparoscopic adjustable gastric banding (LAGB), laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), adjustable gastric banding (AGB), gastric banding (GB), vertical gastric banding (VGB), biliopancreatic diversion (BPD), and silastic ring vertical gastroplasty (SRVG). More than half of bariatric surgery patients have reported sexual dysfunction (SD) [11]. The Female Sexual Function Index (FSFI) [12] and the International Index of Erectile Function (IIEF) [13] are used to measure female and male sexual function, respectively. Women with a total FSFI score ≤26 are categorized as having female sexual dysfunction (FSD). Men who score <26 on the erectile function subscale are diagnosed as having erectile dysfunction (ED). After bariatric surgery, insulin sensitivity is improved by weight loss, and sexual function is expected to improve. Some studies have shown that sexual function in obese patients is improved after bariatric surgery [5, 11, 14–21]. However, one study has shown no improvement in sexual function after LGB, with deterioration of erectile index and orgasmic function when adjusted for time [22]. Furthermore, a study has suggested that surgeons should be cautious about recommending bariatric surgery because the incidence of long-term complications after surgery is high, especially for LGB [23]. Some studies have found that obesity in men is associated with increased estrogens and reduced total testosterone (TT), free testosterone (FT), and sex hormone–binding globulin (SHBG) levels [24]. Few studies have specifically evaluated the effect of bariatric surgery on sex hormone levels in obese patients, and the results are controversial. A randomized controlled trial [19] investigated 10 obese men who accepted lifestyle interventions for 4 months and then underwent gastric bypass with a 20-month follow-up period. The study revealed that there was no impact on hormone levels or sexual function after lifestyle modifications but that TT, FT, and follicle-stimulating hormone (FSH) increased and estradiol (E2) decreased significantly after gastric bypass. Mora et al. [18] found that TT, FT, FSH, and SHBG levels increased after GB and SG. In contrast, luteinizing hormone (LH) and E2 increased, but the increase did not reach statistical significance. The relationships between bariatric surgery and type 2 diabetes mellitus (T2DM), hypertension, heart disease, and other diseases in obese patients have been given a great deal of attention. A meta-analysis found that 78% of 3188 patients with diabetes showed normalization of blood glucose after surgery [25]. A meta-analysis indicated that obese patients experience improvement or resolution of their hypertension after bariatric surgery [26]. In addition, a systematic review clearly illustrated a benefit of bariatric surgery not only on future cardiovascular risk but also on myocardial mass and diastolic function [27]. A recent survey revealed that the number of patients who experienced an improvement in SD after surgery increases exponentially in both genders [28]. Our meta-analysis aimed to obtain a global estimate of the effect of bariatric surgery on sexual function and sex hormone levels in obese patients. 1. Materials and Methods A. Data Sources Data were extracted from PubMed, Medline, and Cochrane databases by two independent investigators using the following Medical Subject Headings terms and keywords: bariatric surgery, sexual function, and sex hormone. All studies in the English language and with human subjects published from 1 January 1990 to 1 December 2016 were included. References of recent systematic reviews were used to identify other potentially relevant studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was used to depict the search strategy (Fig. 1) [29]. Figure 1. View largeDownload slide PRISMA flowchart for studies reporting on sexual function and sex hormone levels in bariatric surgery. Figure 1. View largeDownload slide PRISMA flowchart for studies reporting on sexual function and sex hormone levels in bariatric surgery. B. Study Selection All relevant studies regarding the effect of bariatric surgery on sexual function and sex hormone levels were included, and the findings were then screened and cross-checked. Differences were resolved by discussion. Any lack of information was addressed by contacting the author of the study. The included articles met the following conditions: published in English; adult patients; reported sexual function (FSFI or IIEF) and at least one sex hormone level, including TT, FT, E2, LH, FSH, SHBG, or insulin (blood samples were taken in the morning after an overnight fast and were performed in the early follicular phase of the menstrual cycle for women); follow-up time of at least ≥6 months; and results expressed parameters in terms of mean ± standard deviation. Studies reporting on fertility and pregnancy were excluded if those studies focused on body image, marital satisfaction, or sexual abuse. Publications were excluded if results were expressed as median values. C. Data Extraction An included study had to describe values of FSFI or IIEF and at least one sex hormone level, including TT, FT, E2, LH, FSH, SHBG, and insulin, among obese patients before and after bariatric surgery. Information about the following variables was systematically recorded: study design, sex, age, sample size, surgery type, baseline BMI, and follow-up time. Data describing sexual function and sex hormone levels at 12 months were extracted if the data were available from multiple time points. D. Assessment of Study Quality Considering the characteristics of all included studies, the Newcastle–Ottawa Scale (NOS) (http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp) was specifically used to assess the methodological quality of each study according to the three major domains (the selection of participants, the comparability of the groups, and the exposure ascertainment) of the scoring system. The score ranged between 0 and 9 for each study. A total score of ≥7 indicated high quality, and a total score ≤6 indicated low quality. E. Data Synthesis Continuous variables of sexual function and sex hormone levels were used as results. Summary of evaluation is expressed as the mean difference (MD) with 95% confidence intervals (CIs). P ≤ 0.05 (two-sided) was set as statistical significance. Heterogeneity was estimated with I2 statistics. If I2 > 50%, heterogeneity existed according to the Cochrane handbook [30]. If I2 > 50%, a random effects model was used, and if heterogeneity was not present, a fixed effects model was used. An Egger or Begg test was used to assess publication bias for the included studies >10. Meta-analyses were performed in Review Manager (RevMan version 5.3.5; The Nordic Cochrane Centre, Copenhagen, Denmark) [31] and Stata (version 12.0; StataCorp, College Station, TX) software programs. 2. Results A. Study Selection We searched and then screened 139 potential publications according to the PRISMA guidelines [29]. Seventy-nine publications were excluded because 65 studies did not discuss sexual function or sex hormone levels in obese patients who underwent bariatric surgery, 11 studies were not based on human studies, and 3 studies were published in French. Sixty potential articles have been carried out full-length paper evaluation. However, 12 of these studies were excluded because they reported only sexual function or sex hormone levels result either before or after surgery, and 4 studies were excluded because they used the Impact of Weight on Quality of Life–Lite measure of SD. Moreover, 3 studies were excluded because they used the Brief Male Sexual Function Inventory to evaluate male sexual function, and 5 studies were excluded because the results were expressed as median values. Ultimately, 36 studies were included in the meta-analysis [5, 11, 14–22, 24, 32–55], and the search strategy is shown in Fig. 1. The full text of 12 articles was assessed for the effect of lifestyle modifications on sexual function and sex hormone levels in obese patients [56–66] (Supplemental Table 1 and Supplemental Fig. 1). B. Study Characteristics There were 21 prospective, 2 retrospective, 3 cohort, and 2 observational studies included in our meta-analysis. Table 1 shows the main characteristics of all included studies. Among the studies, 1273 obese patients were evaluated before and after bariatric surgery. The following types of surgery were performed (the numbers in parentheses represent the number of included studies): RYGB (17), BPD (8), LAGB (5), SG (5), LGB (5), LSG (4), LRYGB (4), GB (3), VBG (2), AGB (2), and SRVG (1). Some studies [11, 14, 16, 18, 20, 24, 34–36, 38, 40, 50, 51, 53] included more than one method of surgery. The time to postoperative follow-up ranged from 1 to 115 months. The NOS quality scores of the studies ranged from 6 to 9. Table 1. Studies Included in the Meta-Analysis Study  Design  N  Sex  Mean Age (y)  Study Procedures  Baseline BMI (kg/m2)  Follow-Up (mo)  Outcome Indicators  Ernst et al.,32 2013  N/A  36  F  41.2  RYGB  44.5 ± 0.8  12  3, 4, 8  Assimakopoulos et al.,14 2013  Prospective study  59  F  36  BPD, RYGB, SG  51.9 ± 9.92  12  2  Bond et al.,11 2011  Cohort study  54  F  43.3  LAGB, RYGB  45.1 ± 6.8  6  2  Hernández et al.,15 2012  Prospective study  80  F  43.5  BPD  52.2 ± 8.2  12  2  Olivera et al.,16 2012  Prospective cohort study  36  F  41.3  RYGB, LAGB, LSG  45.76 ± 6.48  37  2  Legro et al.,17 2012  Prospective cohort study  29  F  34.5  RYGB  49 ± 73  12  2, 3, 5, 8  Mora et al.,18 2013  Prospective study  39  M  43.5  LRYGB, LSG  46.90 ± 7.77  12  1, 3, 4, 5, 6, 7, 8  Reis et al.,19 2015  Prospective randomized controlled study  10  M  39.3  GB  55.7 ± 7.8  24  1, 3, 4, 5, 6, 7  Rosenblatt et al.,33 2012  Prospective cohort study  23  M  47.5  RYGB  58.1 ± 12.1  115  1, 3, 4, 5, 6, 7 8, 9  Ranasinghe et al.,22 2010  Retrospective study  34  M  52.8  LGB  47.3 ± 12.67  31  1  Sarwer et al.,34 2014  Prospective cohort study  98  F  41  RYGB, LAGB  44.5 (41.4, 49.7)  12  2, 3, 5, 6, 7, 8  Goitein et al.,20 2015  N/A  34  F  38.4  LSG, LYRGB  44.4 ± 5.5  6  2  Kun et al.,21 2014  Retrospective cohort study  39  M  45.2  RYGB  41.2 ± 5.8  12  1  Sarwer et al.,5 2015  Prospective cohort study  32  M  48  RYGB  45.1 (42.0, 52.2)  12  1, 3, 4, 6, 8  Escobar-Morreale et al.,35 2005  Prospective study  12  F  29.8  BPD, LGB  50.7 ± 7.1  12  3, 4  Rochester et al.,36 2009  Observational cohort study  25  F  36.6  BPD, GB  47.3 ± 5.2  6  6, 7  Alagna et al.,37 2006  N/A  20  M  42  BPD  47.3 ± 13.1  12  3, 5, 6, 7  Calderón et al.,38 2014  N/A  20  M  38  LGB  50.4 ± 8.7  12  3, 4, 5, 6, 7, 8, 9  Calderón et al.,38 2014  N/A  15  M  41  SG, AGB  42.9 ± 2.7  12  3, 4, 5, 6, 7, 8  Hammoud et al.,39 2009  Cohort study  22  M  48.9  RYGB  46.2 ± 0.9  24  3, 4, 5  Pellitero et al.,40 2012  Observational study  33  M  40.5  RYGB, SG  50.3 ± 6.1  12  3, 4, 5, 8  Samavat et al.,24 2014  Prospective cohort study  55  M  42.3  RYGB, LAGB, BPD, SG  46.6 ± 7.4  12  3, 5, 6, 7, 8  Globerman et al.,41 2005  N/A  17  M  38.2  SRVG  44.3 ± 1.7  12  3, 4, 6, 7  Woodard et al.,42 2012  N/A  64  M  48.1  RYGB  48.2 ± 12  12  3  Bastounis et al.,43 1998  Prospective study  19  M  34.7  VBG  57.1 ± 7.4  12  3, 4, 5, 6, 7, 8, 9  Bastounis et al.,43 1998  Prospective study  38  F  34.3  VBG  56.7 ± 7.7  12  3, 4, 5, 6, 7, 8, 9  Legro et al.,44 2015  Prospective cohort study  6  M  37.5  RYGB  48 ± 7  12  5, 8  Samavat et al.,45 2014  Prospective study  76  M  42  LRYGB  47.7 ± 8.2  9  3, 4, 5, 6, 7, 8  Kopp et al.,46 2014  Prospective study  43  F  41  VBG  48 ± 7  17  3, 8, 9  Mihalca et al.,47 2014  Prospective study  28  M  43.1  LSG  50.1 ± 11.19  6  3, 6, 8  Turkmen et al.,48 2014  N/A  9  F  31.4  RYGB  47.2 ± 8.85  12  3, 8  Mingrone et al.,49 2002  Prospective randomized controlled study  15  M  30 to 45  BPD  48.0 ± 5.4  12  8, 9  Mingrone et al.,49 2002  Prospective randomized controlled study  31  F  30 to 45  BPD  48.3 ± 6.3  12  8, 9  Botella-Carretero et al.,50 2013  Prospective study  20  M  40  BPD, LGB, AGB  47.05 ± 5.99  6  3, 4, 5, 6, 7, 8, 9  Aarts et al.,51 2014  Observational study  24  M  43.1  LAGB, LRYGB  46.1 ± 1.3  12  3, 4, 5, 6, 7, 8  Bekaert et al.,52 2015  Cohort study  14  M  51  GB  45.0 ± 8.0  24  3, 4, 5  Boonchaya-Anant et al.,53 2016  Prospective study  29  M  30.8  RYGB, SG  56.8 ± 11.7  6  3, 4, 5, 8  Eid et al.,54 2014  Prospective study  14  F  36.3  RYGB  44.8 ± 1.6  12  3, 4, 6, 7  Dixon et al.,55 2002  N/A  42  F  34  LGB  44.9 ± 7.7  12  3, 8, 9  Study  Design  N  Sex  Mean Age (y)  Study Procedures  Baseline BMI (kg/m2)  Follow-Up (mo)  Outcome Indicators  Ernst et al.,32 2013  N/A  36  F  41.2  RYGB  44.5 ± 0.8  12  3, 4, 8  Assimakopoulos et al.,14 2013  Prospective study  59  F  36  BPD, RYGB, SG  51.9 ± 9.92  12  2  Bond et al.,11 2011  Cohort study  54  F  43.3  LAGB, RYGB  45.1 ± 6.8  6  2  Hernández et al.,15 2012  Prospective study  80  F  43.5  BPD  52.2 ± 8.2  12  2  Olivera et al.,16 2012  Prospective cohort study  36  F  41.3  RYGB, LAGB, LSG  45.76 ± 6.48  37  2  Legro et al.,17 2012  Prospective cohort study  29  F  34.5  RYGB  49 ± 73  12  2, 3, 5, 8  Mora et al.,18 2013  Prospective study  39  M  43.5  LRYGB, LSG  46.90 ± 7.77  12  1, 3, 4, 5, 6, 7, 8  Reis et al.,19 2015  Prospective randomized controlled study  10  M  39.3  GB  55.7 ± 7.8  24  1, 3, 4, 5, 6, 7  Rosenblatt et al.,33 2012  Prospective cohort study  23  M  47.5  RYGB  58.1 ± 12.1  115  1, 3, 4, 5, 6, 7 8, 9  Ranasinghe et al.,22 2010  Retrospective study  34  M  52.8  LGB  47.3 ± 12.67  31  1  Sarwer et al.,34 2014  Prospective cohort study  98  F  41  RYGB, LAGB  44.5 (41.4, 49.7)  12  2, 3, 5, 6, 7, 8  Goitein et al.,20 2015  N/A  34  F  38.4  LSG, LYRGB  44.4 ± 5.5  6  2  Kun et al.,21 2014  Retrospective cohort study  39  M  45.2  RYGB  41.2 ± 5.8  12  1  Sarwer et al.,5 2015  Prospective cohort study  32  M  48  RYGB  45.1 (42.0, 52.2)  12  1, 3, 4, 6, 8  Escobar-Morreale et al.,35 2005  Prospective study  12  F  29.8  BPD, LGB  50.7 ± 7.1  12  3, 4  Rochester et al.,36 2009  Observational cohort study  25  F  36.6  BPD, GB  47.3 ± 5.2  6  6, 7  Alagna et al.,37 2006  N/A  20  M  42  BPD  47.3 ± 13.1  12  3, 5, 6, 7  Calderón et al.,38 2014  N/A  20  M  38  LGB  50.4 ± 8.7  12  3, 4, 5, 6, 7, 8, 9  Calderón et al.,38 2014  N/A  15  M  41  SG, AGB  42.9 ± 2.7  12  3, 4, 5, 6, 7, 8  Hammoud et al.,39 2009  Cohort study  22  M  48.9  RYGB  46.2 ± 0.9  24  3, 4, 5  Pellitero et al.,40 2012  Observational study  33  M  40.5  RYGB, SG  50.3 ± 6.1  12  3, 4, 5, 8  Samavat et al.,24 2014  Prospective cohort study  55  M  42.3  RYGB, LAGB, BPD, SG  46.6 ± 7.4  12  3, 5, 6, 7, 8  Globerman et al.,41 2005  N/A  17  M  38.2  SRVG  44.3 ± 1.7  12  3, 4, 6, 7  Woodard et al.,42 2012  N/A  64  M  48.1  RYGB  48.2 ± 12  12  3  Bastounis et al.,43 1998  Prospective study  19  M  34.7  VBG  57.1 ± 7.4  12  3, 4, 5, 6, 7, 8, 9  Bastounis et al.,43 1998  Prospective study  38  F  34.3  VBG  56.7 ± 7.7  12  3, 4, 5, 6, 7, 8, 9  Legro et al.,44 2015  Prospective cohort study  6  M  37.5  RYGB  48 ± 7  12  5, 8  Samavat et al.,45 2014  Prospective study  76  M  42  LRYGB  47.7 ± 8.2  9  3, 4, 5, 6, 7, 8  Kopp et al.,46 2014  Prospective study  43  F  41  VBG  48 ± 7  17  3, 8, 9  Mihalca et al.,47 2014  Prospective study  28  M  43.1  LSG  50.1 ± 11.19  6  3, 6, 8  Turkmen et al.,48 2014  N/A  9  F  31.4  RYGB  47.2 ± 8.85  12  3, 8  Mingrone et al.,49 2002  Prospective randomized controlled study  15  M  30 to 45  BPD  48.0 ± 5.4  12  8, 9  Mingrone et al.,49 2002  Prospective randomized controlled study  31  F  30 to 45  BPD  48.3 ± 6.3  12  8, 9  Botella-Carretero et al.,50 2013  Prospective study  20  M  40  BPD, LGB, AGB  47.05 ± 5.99  6  3, 4, 5, 6, 7, 8, 9  Aarts et al.,51 2014  Observational study  24  M  43.1  LAGB, LRYGB  46.1 ± 1.3  12  3, 4, 5, 6, 7, 8  Bekaert et al.,52 2015  Cohort study  14  M  51  GB  45.0 ± 8.0  24  3, 4, 5  Boonchaya-Anant et al.,53 2016  Prospective study  29  M  30.8  RYGB, SG  56.8 ± 11.7  6  3, 4, 5, 8  Eid et al.,54 2014  Prospective study  14  F  36.3  RYGB  44.8 ± 1.6  12  3, 4, 6, 7  Dixon et al.,55 2002  N/A  42  F  34  LGB  44.9 ± 7.7  12  3, 8, 9  Outcome indicators: (1) IIEF, (2) FSFI, (3) TT, (4) FT, (5) E2, (6) LH, (7) FSH, (8) SHBG, (9) insulin. View Large C. Bariatric Surgery and Sexual Function Of the 36 studies, 5 studies [5, 18, 19, 21, 22] reported the IIEF of obese men before and after bariatric surgery in 154 of 1273 patients. Based on a fixed effects model, meta-analysis showed a significant increase in IIEF score (MD = 4.84; 95% CI, 2.92 to 6.75; P < 0.00001; Fig. 2A). Seven studies [11, 14–17, 20, 34] reported the FSFI score of obese women before and after bariatric surgery in 369 of 1273 patients. Based on a random effects model, meta-analysis showed that the FSFI score after surgery was higher than the preoperative score, but this increase did not reach statistical significance (MD = 4.10; 95% CI, −0.28 to 8.48; P = 0.07; Fig. 2B). Moreover, assessments of the effects of lifestyle-mediated weight loss on sexual function in obese men showed that bariatric surgery was associated with a greater increase in IIEF than lifestyle modification, but this increase did not reach statistical significance (Supplemental Fig. 2). Figure 2. View largeDownload slide (A) Forest plot of the mean difference of the IIEF in men before and after bariatric surgery. (B) Forest plot of the mean difference of the FSFI in women before and after bariatric surgery. Figure 2. View largeDownload slide (A) Forest plot of the mean difference of the IIEF in men before and after bariatric surgery. (B) Forest plot of the mean difference of the FSFI in women before and after bariatric surgery. D. Bariatric Surgery and Sex Hormone Levels in Obese Men Information about the TT, FT, and E2 levels in the obese men before and after bariatric surgery was available in 18, 12, and 12 studies, respectively. Moreover, data on the LH, FSH, and SHBG levels were available in 12, 11, and 14 studies, respectively. Seventeen studies [5, 18, 19, 33, 37–43, 45, 47, 50–53] reported TT levels in obese men before and after bariatric surgery in 560 of the 1273 patients. Based on a random effects model, meta-analysis showed a significant increase in post–bariatric surgery TT levels (MD = 8.30; 95% CI, 6.92 to 9.68; P < 0.00001; Fig. 3A). Twelve studies [5, 18, 19, 33, 38, 40, 41, 43, 50–53] reported FT levels in obese men before and after bariatric surgery in 295 of 1273 patients. Using a random effects model, meta-analysis showed a significant increase in FT levels (MD = 16.06; 95% CI, 9.33 to 22.79; P < 0.00001; Fig. 3B). Twelve studies [18, 19, 24, 33, 37, 38, 40, 43, 44, 51–53] reported E2 levels in obese men before and after bariatric surgery in 294 of 1273 patients. Based on a random effects model, meta-analysis showed significantly lower E2 levels (MD = −4.49; 95% CI, −6.97 to −2.02; P = 0.0004; Fig. 3C). Twelve studies [18, 19, 24, 33, 37, 38, 41, 43, 45, 47, 50, 51] reported LH levels in obese men before and after bariatric surgery in 353 of 1273 patients. Based on a random effects model, meta-analysis showed a significant increase in LH levels (MD = 1.14; 95% CI, 0.75 to 1.52; P < 0.00001; Fig, 3D). Eleven studies [18, 19, 24, 33, 37, 38, 41, 43, 45, 50, 51] reported FSH levels in obese men before and after surgery in 325 of 1273 patients. Based on a fixed effects model, meta-analysis showed a significant increase in FSH levels (MD = 1.07; 95% CI, 0.75 to 1.40; P < 0.00001; Fig. 3E). Fourteen studies [5, 18, 24, 33, 38, 40, 43–45, 47, 49–51, 53] reported SHBG levels in obese men before and after bariatric surgery in 421 of the 1273 patients. Based on a random effects model, meta-analysis showed a significant increase in SHBG levels (MD = 22.32; 95% CI, 16.12 to 28.51; P < 0.00001; Fig. 3F). Five studies [33, 38, 43, 49, 50] reported insulin levels in obese men before and after bariatric surgery in 112 of 1273 patients. Based on a random effects model, meta-analysis showed a significant decrease in insulin levels (MD = −138.97; 95% CI, −181.82 to −96.12; P < 0.00001; Fig. 3G). When we considered data for TT, FT, E2, SHBG, and insulin levels, bariatric surgery showed a greater improvement than lifestyle interventions (Supplemental Fig. 3). Figure 3. View largeDownload slide (A) Forest plot of the mean difference in TT levels in men before and after bariatric surgery. (B) Forest plot of the mean difference in FT levels in men before and after bariatric surgery. (C) Forest plot of the mean difference in E2 levels in men before and after bariatric surgery. (D) Forest plot of the mean difference in LH levels in men before and after bariatric surgery. (E) Forest plot of the mean difference in FSH levels in men before and after bariatric surgery. (F) Forest plot of the mean difference in SHBG levels in men before and after bariatric surgery. (G) Forest plot of the mean difference in insulin levels in men before and after bariatric surgery. Figure 3. View largeDownload slide (A) Forest plot of the mean difference in TT levels in men before and after bariatric surgery. (B) Forest plot of the mean difference in FT levels in men before and after bariatric surgery. (C) Forest plot of the mean difference in E2 levels in men before and after bariatric surgery. (D) Forest plot of the mean difference in LH levels in men before and after bariatric surgery. (E) Forest plot of the mean difference in FSH levels in men before and after bariatric surgery. (F) Forest plot of the mean difference in SHBG levels in men before and after bariatric surgery. (G) Forest plot of the mean difference in insulin levels in men before and after bariatric surgery. E. Bariatric Surgery and Sex Hormone Levels in Obese Women There are limited studies on sex hormone levels in obese women who underwent bariatric procedures. Information about TT, FT, and E2 levels in obese women was available in 8, 4, and 2 studies, respectively. In addition, data for LH, FSH, and SHBG levels were usable in 4, 4, and 7 studies, respectively. In total, we retrieved 8 studies [32, 34, 35, 43, 46, 48, 54, 55] reporting TT levels in obese women preoperatively and postoperatively in 291 of 1273 patients. Based on a random effects model, meta-analysis indicated a significant decrease in postoperative TT levels (MD = −0.71; 95% CI, −0.84 to −0.58; P < 0.00001; Fig. 4A). Four studies [32, 35, 43, 54] reported FT levels in obese women before and after surgery in 100 of 1273 patients. Based on a random effects model, meta-analysis indicated a decrease in the postsurgical FT levels, but this decrease did not reach statistical significance (MD = −13.65; 95% CI, −28.82 to 1.53; P = 0.08; Fig. 4B). Two studies [34, 43] assessed E2 levels in obese women before and after bariatric surgery in 136 of 1273 patients. Based on a fixed effects model, the meta-analysis indicated a significant decrease in postoperative E2 levels (MD = −25.13; 95% CI, −36.93 to −13.32; P < 0.0001; Fig. 4C). Four studies [34, 36, 43, 54] evaluated LH levels in obese women before and after surgery in 156 of 1273 patients. Based on a random effects model, meta-analysis showed significantly increased LH levels (MD = 5.73; 95% CI, 0.15 to 11.30; P = 0.04; Fig. 4D). Four studies [34, 36, 43, 54] reported preoperative and postoperative FSH levels in obese women in 156 of 1273 patients. Based on a random effects model, meta-analysis showed a significant increase in FSH levels (MD = 3.79; 95% CI, 0.71 to 6.88; P = 0.02; Fig. 4E). However, the FSH levels in obese women showed a significant reduction after lifestyle modification (Supplemental Fig. 4D). Seven studies [32, 34, 43, 46, 48, 49, 55] assessed SHBG levels in obese women before and after bariatric surgery in 296 of 1273 patients. Based on a random effects model, meta-analysis showed a significant increase in SHBG levels (MD = 31.84; 95% CI, 20.24 to 43.44; P < 0.00001; Fig. 4F). Four studies [43, 46, 49, 55] reported insulin levels in obese women before and after bariatric surgery in 154 of 1273 patients. Based on a random effects model, meta-analysis reported a significant decrease in insulin levels (MD = −93.36; 95% CI, −119.86 to −66.86; P < 0.00001; Fig. 4G). When we considered data for TT, LH, SHBG, and insulin levels in obese women, both lifestyle intervention and bariatric surgery showed an improvement, but bariatric surgery was significantly more effective than lifestyle intervention (Supplemental Fig. 4A, 4B, 4C, and 4E). Figure 4. View largeDownload slide (A) Forest plot of the mean difference in TT levels in women before and after bariatric surgery. (B) Forest plot of the mean difference in FT levels in women before and after bariatric surgery. (C) Forest plot of the mean difference in E2 levels in women before and after bariatric surgery. (D) Forest plot of the mean difference in LH levels in women before and after bariatric surgery. (E) Forest plot of the mean difference in FSH levels in women before and after bariatric surgery. (F) Forest plot of the mean difference in SHBG levels in women before and after bariatric surgery. (G) Forest plot of the mean difference in insulin levels in women before and after bariatric surgery. (H) Forest plot of the mean difference in TT levels in women with PCOS before and after bariatric surgery. (I) Forest plot of the mean difference in FT levels in women with PCOS before and after bariatric surgery. Figure 4. View largeDownload slide (A) Forest plot of the mean difference in TT levels in women before and after bariatric surgery. (B) Forest plot of the mean difference in FT levels in women before and after bariatric surgery. (C) Forest plot of the mean difference in E2 levels in women before and after bariatric surgery. (D) Forest plot of the mean difference in LH levels in women before and after bariatric surgery. (E) Forest plot of the mean difference in FSH levels in women before and after bariatric surgery. (F) Forest plot of the mean difference in SHBG levels in women before and after bariatric surgery. (G) Forest plot of the mean difference in insulin levels in women before and after bariatric surgery. (H) Forest plot of the mean difference in TT levels in women with PCOS before and after bariatric surgery. (I) Forest plot of the mean difference in FT levels in women with PCOS before and after bariatric surgery. Subgroup analysis with PCOS, a common complication among obese patients, was performed in obese women. In three studies [35, 48, 54], TT levels in 62 obese women with PCOS before and after bariatric surgery showed a significant decrease (MD = −0.69; 95% CI, −1.19 to −0.18; P = 0.008; Fig. 4H), but the decrease was not significant compared with that of all included obese women. Two studies [35, 54] showed a greater reduction of FT levels in obese women with PCOS than in all included obese women, but this reduction did not reach statistical significance (MD = −23.58; 95% CI, −50.03 to 2.88; P = 0.08; Fig. 4I). Because only one of three studies reported LH, FSH, and SHBG levels in obese women with PCOS before and after bariatric surgery, the data were insufficient to conduct subgroup analyses. F. Publication Bias Assessment Publication bias was assessed by Egger publication bias plots in the meta-analysis regarding the changes in TT (18 studies), FT (12 studies), and E2 levels (12 studies) in obese men (Fig. 5A, 5B, and 5C). The P values of the Begg and Egger tests for TT (0.484 and 0.541, respectively), FT (0.246 and 0.111, respectively), and E2 (0.760 and 0.515, respectively) suggested that there was no significant publication bias. Similarly, publication bias was evaluated by Egger publication bias plots in the meta-analysis regarding the changes in LH (12 studies), FSH (11 studies), and SHBG levels (14 studies) in obese men (Fig. 5D, 5E, and 5F). The P values of the Begg and Egger tests for LH (0.428 and 0.668, respectively), FSH (0.537 and 0.142, respectively), and SHBG (0.373 and 0.002, respectively), suggested a lack of significant publication bias, except for the Egger test of SHBG. The reasons for different statistical significances between these two test methods may be small study size, including SHBG, or the number of included studies. Figure 5. View largeDownload slide (A) Egger test assessing publication bias for TT levels in obese men. (B) Egger test assessing publication bias for FT levels in obese men. (C) Egger test assessing publication bias for E2 levels in obese men. (D) Egger test assessing publication bias for LH levels in obese men. (E) Egger test assessing publication bias for FSH levels in obese men. (F) Egger test assessing publication bias for SHBG levels in obese men. Figure 5. View largeDownload slide (A) Egger test assessing publication bias for TT levels in obese men. (B) Egger test assessing publication bias for FT levels in obese men. (C) Egger test assessing publication bias for E2 levels in obese men. (D) Egger test assessing publication bias for LH levels in obese men. (E) Egger test assessing publication bias for FSH levels in obese men. (F) Egger test assessing publication bias for SHBG levels in obese men. 3. Discussion Our meta-analysis showed that the IIEF in obese men and the FSFI in obese women improved after bariatric surgery, but the improvement was statistically significant only in men. These results were consistent with most current systematic reviews of changes in sexual dysfunction after bariatric surgery [28]. The current meta-analysis showed a significant increase in TT, FT, LH, FSH, and SHBG levels and a reduction in E2 levels after bariatric surgery in obese men. In contrast, the TT and E2 levels in obese women significantly decreased, whereas LH, FSH, and SHBG levels significantly increased. The FT levels were also decreased in obese women, but these decreases were not significant. The normalization of sex hormones may be one of the mechanisms contributing to the advantageous effects of surgery in morbid obesity patients. The relationship between the improvement of sexual dysfunction and the sex hormone changes did not achieve consensus. Hammoud et al. [39] found that changes in sex hormones and sexual function improve insulin resistance and inflammation, and they also reported that resolution of diabetes and hypertension occurs after RYGB. Our meta-analysis suggested that bariatric surgery is related to increased insulin sensitivity in both sexes, which may be one of the factors contributing to the improvement of sex hormone levels. A previous study [50] has reported that circulating testosterone in obese men increases after BPD, LGB, or AGB in parallel with a decrease in insulin resistance. However, no studies have reported the independent contribution of each factor. Ranasinghe et al. [22] found that obese male patients displayed elevated TT, FT, and SHBG levels and improved IIEF scores but that erectile function scores were reduced after LGB, suggesting incomplete functional restoration. Relapsing obesity and recurring comorbidities might explain such an outcome. Two prospective cohort studies [17, 34] have shown no statistical evidence of the changes in FSFI and hormones after surgery by correlation of regression. However, a prospective observational study [18] found that the increase in the IIEF score at 1 year after surgery was beyond the parallel improvement of hormone levels by a multivariate regression. It is important to note that it is difficult to account for all risk factors that may contribute to sexual function, such as psychological factors and metabolic changes, when determining causality. PCOS is a common endocrine disorder in women of reproductive age. A recent study [67] has shown that surgically induced weight loss not only may reduce hirsutism in women but also may resolve menstrual and ovulatory dysfunction in severely obese patients with PCOS after bariatric surgery. Consistently, our meta-analysis showed sustained and marked weight loss after bariatric surgery with decreases in TT and FT levels, although FT levels only showed a trend, possibly because of the limited quantity of the included studies. These effects might also contribute to restoration of fertility in these women. A previous study reported that weight loss by surgery may improve fertility rates in women [68], and it also suggested that pregnancy is delayed 1 to 2 years after bariatric surgery with proper nutritional and obstetric support. Significant increases in TT, FT, FSH, and SHBG levels have the potential to improve fertility in severely obese men. However, studies evaluating spermatogenesis after surgery have had inconsistent results. Some studies have suggested adverse effects on semen parameters [69–71], whereas some prospective studies have performed serial semen analyses and showed normal ranges for most parameters [19, 44]. A more recent study [72] has shown that sperm concentration is increased in men with azoospermia and oligospermia after surgery, suggesting that weight loss may improve sperm quality. Weight loss alone may be helpful in obesity-associated SD and is strongly recommended for the management of obesity. Lifestyle interventions that include diet and exercise have a short-term effect because weight loss is difficult to obtain by lifestyle modifications, and the weight is easily regained when the lifestyle interventions are not sustained [8, 73]. Bariatric surgery is a better and longer-lasting weight loss alternative for severely obese patients. Our meta-analysis indicated that bariatric surgery is associated with a greater increase in TT, FT, and SHBG levels and a greater decrease in E2 than lifestyle interventions in obese men. In obese women, however, our meta-analysis showed that levels of TT, FT, and E2 after bariatric surgery are more significantly decreased and that the levels of LH, FSH, and SHBG are more significantly increased in comparison with lifestyle modifications. These results may be caused by the greater weight loss achieved by surgery. This meta-analysis was not without limitations. Several limitations that prevent achievement of definite conclusions should be considered. First, there was significant heterogeneity in the outcome analyses, except for IIEF and FSH in men and E2 in women. This heterogeneity may result from the absence of randomized controlled trials, different research designs, and variable research populations. Second, another limitation was the patient self-reporting, which was completed before and after surgery, because patients may have felt embarrassed when completing the sexual function questionnaires. Third, our meta-analysis measured SD only by IIEF in men and by FSFI in women, but our meta-analysis did not include the Brief Male Sexual Function Inventory [74], which consists of an 11-item questionnaire. Also, our meta-analysis did not include the Impact of Weight on Quality of Life-Lite, which takes into account other aspects of self-esteem and work [75]. Fourth, the fact that hormonal assays and reference values often are not comparable imposed a limitation on the generalization of our results. Fifth, we extracted the results at the 12-month time point only if parameters were evaluated at several different time points, which provided a conservative estimate of the effect of bariatric surgery on sexual function and sex hormones. The follow-up period after bariatric surgery in many studies was short, and the possibility of a relapse of obesity-associated sexual dysfunction and changes in sex hormone levels in the long term was not explored. A limitation to this method was that the full effect of bariatric surgery on sexual function and sex hormones may not have been realized. Finally, the small sample size of some studies was a limitation that especially affected the studies in women and the studies addressing the changes in sexual function after bariatric surgery. In conclusion, this meta-analysis showed that bariatric surgery significantly improves sexual function in men but that a more limited degree of improvement is achieved in women. In obese male patients who underwent bariatric surgery, the levels of the sex hormones TT, FT, LH, FSH, and SHBG significantly increased, and the level of E2 decreased. In obese female patients, the levels of the sex hormones TT, FT, and E2 decreased, but the levels of LH, FSH, and SHBG increased. Future studies should be performed to elucidate the mechanism of the improved sexual function in obese patients after bariatric surgery. Because of the limited quality and quantity of the included studies, more high-quality studies are needed to verify our conclusion about the sex hormone levels in obese female patients. Abbreviations: AGB adjustable gastric banding BMI body mass index BPD biliopancreatic diversion CI confidence interval E2 estradiol ED erectile dysfunction FSD female sexual dysfunction FSFI Female Sexual Function Index FSH follicle-stimulating hormone FT free testosterone GB gastric banding IIEF International Index of Erectile Function LAGB laparoscopic adjustable gastric banding LGB laparoscopic gastric banding LH luteinizing hormone LRYGB laparoscopic Roux-en-Y gastric bypass LSG laparoscopic sleeve gastrectomy MD mean difference NOS Newcastle–Ottawa Scale PCOS polycystic ovarian syndrome PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analysis RYGB Roux-en-Y gastric bypass SD sexual dysfunction SG sleeve gastrectomy SHBG sex hormone–binding globulin SRVG silastic ring vertical gastroplasty T2DM type 2 diabetes mellitus TT total testosterone VGB vertical gastric banding. Acknowledgments Financial Support: Natural Science Foundation of China (nos. 81770848 and 81170774) to J.W., Natural Science Foundation of Fujian Province (nos. 2015Y0008 and 2016Y9006) to J.W., and Fujian provincial health system in the youth personnel training project financing plan (2014-ZQN-ZD-1) to J.W. Disclosure Summary: The authors have nothing to disclose. References and Notes 1. World Health Organization. Obesity and overweight fact sheet. World Health Organization Web site. http://www.who.int/mediacentre/factsheets/fs311/en/. Accessed 15 July 2016. 2. Janik MR, Bielecka I, Paśnik K, Kwiatkowski A, Podgórska L. Female sexual function before and after bariatric surgery: a cross-sectional study and review of literature. Obes Surg . 2015; 25( 8): 1511– 1517. Google Scholar CrossRef Search ADS PubMed  3. Mozafari M, Khajavikhan J, Jaafarpour M, Khani A, Direkvand-Moghadam A, Najafi F. Association of body weight and female sexual dysfunction: a case control study. 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Google Scholar CrossRef Search ADS PubMed  Copyright © 2018 Endocrine Society This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/).

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Journal of the Endocrine SocietyOxford University Press

Published: Feb 1, 2018

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